Combination atezolizumab, bevacizumab, pemetrexed and carboplatin for metastatic EGFR mutated NSCLC after TKI failure

Lam, Tai Chung; Tsang, Kwt; Choi, H.C.; Lee, V.H.; Lam, Ka-On; Chiang, Chi‐Lu; So, Tsz Him; Chan, Wendy; Nyaw, S.F.; Lim, Farah Louise; Lau, James Siu Ki; Chik, Jeannie; Kong, F.M.; Lee, A.W.

doi:10.1016/j.lungcan.2021.07.004

Cited by 51 publications

(39 citation statements)

References 47 publications

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Section: Discussionmentioning

confidence: 99%

“…Previous single-arm studies on ICI-based combination regimens in EGFR-mutant NSCLC patients after EGFR TKI failure have reported inconsistent results ( 17 – 19 ). The CT 18 study ( 18 ) and other studies using a combination approach of ICI with chemotherapy have exhibited survival benefits ( 16 , 17 ), which was also observed in our study, whereas a study with camrelizumab plus apatinib achieved inferior outcome ( 19 ). Basic studies support that chemotherapy, antiangiogenic drugs, and radiotherapy exert synergistic effects with ICI via positive regulation of the immune system, changing the tumor immune microenvironment, and releasing tumor neoantigens ( 28 – 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies concerning gene wild-type NSCLC have indicated that the earlier the use of ICIs, the better the outcome maybe ( 33 , 34 ). Some studies on EGFR-mutant NSCLC after EGFR TKI failure recruited patients without prior palliative chemotherapy ( 17 , 18 ), whereas a study of camrelizumab plus apatinib ( 19 ) including patients in the later setting exhibited lower RR and shorter PFS. Our study showed that front-line administration of ICI after EGFR-TKI resistance was more beneficial in terms of PFS and OS.…”

Section: Discussionmentioning

confidence: 99%

“…This four-drug regimen owned an incidence of grade 3 to 4 treatment-related adverse events of 57% ( 16 ). Two studies with a combination approach have reported promising results on response rate (RR) and survival ( 17 , 18 ), while flaws exist due to the small sample size and insufficient information on patients with T790M. Another study with ICI combination treatment got a worse outcome with an objective response rate (ORR) of 18.6% and a median progression-free survival (mPFS) of 2.8 months ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

Tian

et al. 2021

Front. Oncol.

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BackgroundData on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors.Materials and MethodsRelevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors.ResultsA total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05).ConclusionsTaken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

Tian

et al. 2021

Front. Oncol.

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“…The mutations in the KRAS gene can predict the efficiency of EGFRtyrosine kinase inhibitors [42]. Recently, it was observed that most patients that developed resistance to TKIs have different EGFR mutations [43,44]. Mutations in BRAF can be correlated to response to BRAF/MEK inhibitors in NSCLC patients [45][46][47], while PIK3CA mutations could render SCLC patients sensible to triciribine treatment [48].…”

Section: Ngs In Lung Cancer Diagnosismentioning

confidence: 99%

Next Generation Sequencing Technology in Lung Cancer Diagnosis

Căinap

Bălăcescu

Căinap

et al. 2021

Biology

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Lung cancer is still one of the most commonly diagnosed cancers, and one of the deadliest. The high death rate is mainly due to the late stage of diagnosis and low response rate to therapy. Previous and ongoing research studies have tried to discover new reliable and useful cbiomarkers for the diagnosis and prognosis of lung cancer. Next generation sequencing has become an essential tool in cancer diagnosis, prognosis, and evaluation of the treatment response. This article aims to review the leading research and clinical applications in lung cancer diagnosis using next generation sequencing. In this scope, we identified the most relevant articles that present the successful use of next generation sequencing in identifying biomarkers for early diagnosis correlated to lung cancer diagnosis and treatment. This technique can be used to evaluate a high number of biomarkers in a short period of time and from small biological samples, which makes NGS the preferred technique to develop clinical tests for personalized medicine using liquid biopsy, the new trend in oncology.

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Potential therapies targeting nuclear metabolic regulation in cancer

Chen,

Xu,

Liu

et al. 2023

MedComm

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The interplay between genetic alterations and metabolic dysregulation is increasingly recognized as a pivotal axis in cancer pathogenesis. Both elements are mutually reinforcing, thereby expediting the ontogeny and progression of malignant neoplasms. Intriguingly, recent findings have highlighted the translocation of metabolites and metabolic enzymes from the cytoplasm into the nuclear compartment, where they appear to be intimately associated with tumor cell proliferation. Despite these advancements, significant gaps persist in our understanding of their specific roles within the nuclear milieu, their modulatory effects on gene transcription and cellular proliferation, and the intricacies of their coordination with the genomic landscape. In this comprehensive review, we endeavor to elucidate the regulatory landscape of metabolic signaling within the nuclear domain, namely nuclear metabolic signaling involving metabolites and metabolic enzymes. We explore the roles and molecular mechanisms through which metabolic flux and enzymatic activity impact critical nuclear processes, including epigenetic modulation, DNA damage repair, and gene expression regulation. In conclusion, we underscore the paramount significance of nuclear metabolic signaling in cancer biology and enumerate potential therapeutic targets, associated pharmacological interventions, and implications for clinical applications. Importantly, these emergent findings not only augment our conceptual understanding of tumoral metabolism but also herald the potential for innovative therapeutic paradigms targeting the metabolism–genome transcriptional axis.

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Combination atezolizumab, bevacizumab, pemetrexed and carboplatin for metastatic EGFR mutated NSCLC after TKI failure

Cited by 51 publications

References 47 publications

Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

Next Generation Sequencing Technology in Lung Cancer Diagnosis

Potential therapies targeting nuclear metabolic regulation in cancer

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